TGF-β inhibition restores hematopoiesis and immune balance via bone marrow EPCs in aplastic anemia

作者：Xinyan Zhang, Liping Guo, Yazhe Wang, Jinsong Jia, Liang Mi, Meng-Zhu Shen, Zhenkun Wang, Zhiwei Zhang, Chenyuan Li, Zhong‐Shi Lyu, Tong Xing, Yuanyuan Zhang, Xiao‐Jun Huang, Yuan Kong · 发表于：Experimental & Molecular Medicine · 年份：2025 · DOI：10.1038/s12276-025-01483-4 · 被引用次数：7 · 研究领域：Hematopoietic Stem Cell Transplantation、Acute Myeloid Leukemia Research、Lymphatic System and Diseases

Aplastic anemia (AA) is a life-threatening bone marrow (BM) failure syndrome characterized by pancytopenia. Recent studies revealed that dysfunctional endothelial progenitor cells (EPCs), critical components of the BM microenvironment, are involved in hematopoietic-dysfunction-related diseases, including AA. However, the mechanism underlying EPC damage in AA remains unknown. Here we find that transforming growth factor-β (TGF-β) signaling is hyperactive in dysfunctional AA EPCs with impaired hematopoietic support and immune regulatory ability, and TGF-β inhibition promotes hematopoiesis and immune rebalance by repairing dysfunctional EPCs. Through impaired EPC and AA murine models, we validated that TGF-β inhibition restores EPC dysfunction to improve hematopoiesis and immune status in vitro and in vivo. RNA sequencing and real-time quantitative polymerase chain reaction provided further validation. These results indicate that dysfunctional BM EPCs with hyperactive TGF-β signaling are involved in AA. TGF-β inhibition promotes multilineage hematopoiesis recovery and immune balance by repairing dysfunctional EPCs, providing a potential therapeutic strategy for AA.